Our goal is to evaluate the use of ultrasound to detect small regions of increased vascular density and altered blood flow and to quantify small changes in these parameters due to effects of new anti-angiogenic drugs. Regions containing intravascular contrast agents are identified using a new ultrasound strategy that combines subharmonic and phase inversion imaging. The contrast agent is repeatedly destroyed in order to estimate the time required for local replenishment. Parameters are estimated based on this strategy and include measures of the spatial extent of flow, the spatial integral of flow, and the time required for 80% replenishment. In a study of 25 tumors, we first demonstrate that regions of viable tumor as small as 1 mm, as verified by histology, can be detected and show similar morphology to images acquired with computed tomography (CT). The spatial mapping of vessels with ultrasound is superior to contrast enhanced computed tomography due to the intravascular distribution of ultrasound contrast agents. Estimation of the time to 80% replenishment was conducted on kidney and tumor data and is a robust parameter not altered by attenuation. Mean times to 80% replenishment of 1–5 s were estimated for the kidney cortex and mean times of 6–14 s were observed for viable tumor tissue. This broad range of replenishment times is indicative of abnormal tumor vascular density and tortuosity. Changes in flow parameters with anti-angiogenic therapy are significant beginning at 48 hours post-treatment.
Acknowledgement
Supported by NH CA 76062.